Stem Cell–Niche Networks in Ageing and Disease

Our research interest

Our research is focused on understanding the molecular and functional interactions between hematopoietic stem cells (HSCs) and the bone marrow niche. We primarily use the most plastic niche cell population, mesenchymal stroma cells (MSCs), to model HSC - stroma cell interactions in vitro. We are specifically interested in understanding the role of MSCs in acute myeloid leukaemia (AML), and how changes in HSC-niche interactions during ageing might contribute to leukemic transformation.

We are combining computational biology, multiomics methods, co-culture systems of primary human cells, and xenotransplantations to study the mutual impact of the different cell types on each other during ageing and leukemia development.

Background

Bone marrow harbours different types of stem cells comprising HSCs, which give rise to all blood cells, and MSCs, which can differentiate into different stroma cell types. MSCs play a pivotal role in maintaining normal HSC functions such as survival, quiescence, proliferation and differentiation.

Our previous work has focused on understanding the pathogenesis of AML. AML is characterized by a rather small number of disease inducing mutations and multiple epigenetic changes. Results from our groups and others point towards the niche as an essential player in AML pathogenesis. Interactions between leukemic stem cells and the niche are likely to impact on disease initiation, maintenance and therapy response.

Goals

Our research focuses on three major aspects of HSC - niche interactions:

Role of ageing-related changes in stem cell- niche interactions in the development of haematological malignancies

Stem cell - niche communication in genetically defined AML subgroups.

The differential impact of distinct sources of donor HSCs on the recipient bone marrow niche